Apolipoprotein D is a 29-kDa glycoprotein which is primarily associated with the high density lipoproteins (HDL) in human plasma. Apolipoprotein D is classified as belonging to the lipocalin family, on the basis of its primary structure. The apolipoprotein D gene is expressed in various tissues, with high levels expression in the adrenal gland, pancreas, kidneys, placenta, spleen, lungs, ovaries, testes, brain, peripheral nerves, and cerebrospinal fluid. Apolipoprotein D is also found in apocrine axillary secretions. Furthermore, apolipoprotein D was identified as the major component of the mammary cyst fluid from women with breast gross cystic disease.
Apolipoprotein D is degraded by proteases present in the living body or proteases produced by Brevibacterium epiderumidis, a resident skin flora.
Apolipoprotein D can bind various molecules such as cholesterol, steroid hormone, bilirubin, and arachidonic acid, depending on the conditions or the tissue (e.g., nerves) or organ. While neither its role nor its physiological ligand has been clearly identified, it is suggested that apolipoprotein D participates in maintenance and repair within the nervous system as a transporter of such molecules. (see for example, Eric Rassart et al., Biochimica et Biophysica Acta. 1482: 185–198, 2000).
It has been known that decrease can be found in total membrane phospholipids content, arachidonic acid (an essential fatty acid) content, cholesteryl esters in membranes from erythrocytes, red blood cells, and fibroblasts of schizophrenic patients. In addition, it has also been found that apolipoprotein D levels were significantly decreased in serum samples from schizophrenic patients as compared with normal subjects. (see for example, Thomas E A et al., Proc. Natl. Sci. USA, 98: 4066–4071, 2001).
Therefore, by suppressing degradation of apolipoprotein D to prevent decreasing of apolipoprotein D levels, schizophrenia or other diseases caused by denaturation or cell damage in the nervous system, such as Alzheimer's disease, Niemann-Pick disease type C (NPC), and Unverrichit-Lundborg disease can be effectively prevented or treated.